1. Field of the Invention
The present invention relates to drug delivery. More particularly, the present invention relates to methods and apparatus for delivering agents to mucosal and other tissue surfaces, in the presence of capnic gases, particularly for the treatment of rhinitis.
Drug delivery to mucosal surfaces, such as the mucosa of the nose, is well known. While in some cases drugs delivered to the nose and other mucosal surfaces are intended to have local effect, more often such transmucosal drug delivery is intended for systemic administration. In either case, penetration of the drug into or through the mucosa is limited by the ability of the particular drug to pass into or through the mucosal cell structure. Such resistance from the mucosal cell structure can result in slowing of the delivery, the need to use higher dosages of the drug, or in the case of larger molecules, the inability to deliver via a nasal or other mucosal route.
A walk through the cold and allergy section of any pharmacy quickly reveals that there is wide spread interest in remedies for relieving symptoms commonly associated with allergies, colds, asthma, and other common ailments which have symptoms of rhinitis e.g., runny noses and watery eyes. The commonly available therapies include oral medicines, nasal sprays, oral inhalers, nasal inhalers, eye drops, and nose drops, and probably other devices and approaches that have been developed over the years. Still more possible therapies are available from the pharmacy with a prescription from a patient's doctor (e.g., injectables, inhalables). Despite the very large number of therapies which are available, no one therapy meets all patient needs, and many of the therapies suffer from very significant shortcomings. For example, present day therapies are slow-acting, may have numerous adverse side effects (e.g., drowsiness, rebound congestion from decongestant overuse, dizziness, sedation, addiction, and numerous others), have low efficacy, and are contraindicated for a large portion of patients (e.g., those with hypertension, coronary artery disease, cerebrovascular disease, peptic ulcers, pregnancy, concurrent medications that would interact, children, elderly, and others). Suffice it to say that there is a continuing interest in providing improved methods and apparatus for treating such common symptoms and ailments.
Very recently, the use of carbon dioxide and other capnic gases alone and in combination with other gases has been proposed for the treatment of rhinitis and other conditions. The carbon dioxide is preferably delivered to nasal or other mucosa without inhalation. It is believed that the carbon dioxide may cause an intracellular acidosis which inhibits the release of calcitonin gene-related peptide (CGRP) and other neuropeptides which in turn reduces nasal symptoms of rhinitis. It has also been found that the onset of relief with carbon dioxide is usually much more rapid than that achieved with antihistamines, intranasal corticosteroids, leukotriene antagonists, and other drug therapies.
Despite the promise of conventional drug therapies and the newer delivery of capnic gases, neither therapy is effective in all individuals and neither therapy is entirely effective in relieving rhinitis and associated symptoms in all circumstances. It would thus be desirable to provide improved methods and systems for treating rhinitis. In particular, it would be desirable to provide treatments which are more effective, more rapid, more long-lasting, and/or which have other benefits when compared to the administration of either known rhinitis drugs or capnic gases alone.
2. Description of Background Art
Inhalation devices, systems and methods for delivering carbon dioxide and other gases and aerosols to patients, with and without co-delivery of a drug are described in U.S. Pat. Nos. 3,776,227; 3,513,843; 3,974,830; 4,137,914; 4,554,916; 5,262,180; 5,485,827; 5,570,683, 6,581,539; and 6,652,479. While some methods and devices provide for co-delivery of a drug and carbon dioxide or other gases, the purpose is usually not potentiation. For example, carbon dioxide may be used as a safe propellant, as shown in Wetterlin, U.S. Pat. No. 4,137,914. See also copending application Ser. Nos. 09/614,389, 10/666,947, and 10/666,562; the full disclosures of which are incorporated herein by reference.
Additional background art may be found in the following references: Guyton A C, Hall J E. Textbook of Medical Physiology. Ninth Ed., W.B. Saunders Co., Philadelphia, 1996; Tang A, Rayner M, Nadel J. “Effect of CO2 on serotonin-induced contraction of isolated smooth muscle,” Clin Research 20:243, 1972; Qi S, Yang Z, He B. “An experimental study of reversed pulmonary hypertension with inhaled nitric oxide on smoke inhalation injury,” Chung Hua Wai Ko Tsa Chih 35(1):56-8, January 1997; Loh E, Lankford E B, Polidori D J, Doering-Lubit E B, Hanson C W, Acker M A. “Cardiovascular effects of inhaled nitric oxide in a canine model of cardiomyopathy,” Ann Thorac Surg 67(5): 13 80-5, May 1999; Pagano D, Townend J N, Horton R, Smith C, Clutton-Brock T, Bonser RS. “A comparison of inhaled nitric oxide with intravenous vasodilators in the assessment of pulmonary haemodynamics prior to cardiac transplantation,” Eur J Cardiothorac Surg 10(12):1120-6, 1996; and Sterling G, et al. “Effect of CO2 and pH on bronchoconstriction caused by serotonin vs. acetylcholine,” J of Appl Physiology, vol. 22, 1972.